We request funds for a new inductively coupled plasma mass spectrometer (ICP-MS) interfaced to a high- performance liquid chromatography (HPLC) system to be located at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH). ICP-MS is a powerful analytical tool for the detection and quantification of trace elements in a broad range of sample types and is widely accepted as the method of choice for elemental analysis. Modern instrumentation can analyze up to 60 elements simultaneously with a dynamic range spanning 9 orders of magnitude from parts per trillion to parts per thousand. An HPLC interface enables speciation of metal or metalloid analytes in complex matrices like blood plasma or tissue homogenate. The dual mission of the Martinos Center is technology development and translational research involving advanced imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography, optical imaging, and magnetoencephalography. Accurate elemental analysis underpins much of this work. For instance in molecular imaging probe development, quantitative elemental analysis is used to characterize the probes, quantify their distribution, pharmacokinetics, and metabolism in tissue. For imaging of metal ion homeostasis, ICP-MS provides a crucial gold standard. Development of metal-based therapeutics benefits tremendously from HPLC-ICP-MS for metabolism studies. Contrast agents are widely used in the development of quantitative in vivo imaging techniques, e.g. perfusion, permeability, blood volume measurements; ex vivo elemental analysis of these contrast agents can serve to calibrate and validate these methodologies. The requested instrumentation will be administered as a shared resource for the Martinos center, the larger MGH research community, as well as other institutions in the greater Boston area. The Principle Investigator and Advisory Committee will ensure both equitable and cost-effective operation of this system. The acquisition of this HPLC-ICP-MS will greatly benefit our research community and we expect it will play an essential role in driving many new discoveries pertaining to a host of medically related issues including cancer, diabetes, drug addiction, Alzheimer's disease, heart disease, liver disease, stroke, and neural plasticity. PUBLIC HEALTH REELEVANCE: Funds are requested for an elemental analyzer that will allow quantification and distribution of metals and metalloids in biological tissue. The analyses enabled by this instrument will underpin NIH-funded research projects in cancer, heart disease, diabetes, addiction research, Alzheimer's disease, and neuroplasticity.